Fig. 1

IGF1 signaling pathway is activated in response to nutrient deprivation and potentially regulated by miR-15a and Fra-2 in PDAC. a Venn diagram showing the number of molecular pathways enriched in nutrient deprived PDAC cells (purple) and potentially upregulated by miR-15a downregulation (green) and Fra-2 expression (blue) in PDAC patients from the TCGA dataset (n = 176). For nutrient deprivation (purple), data were obtained by performing ingenuity pathway analysis (IPA®) on the overexpressed genes in AsPC-1 and MIA PaCa-2 cell lines, cultured in nutrient deprivation (0% FBS) for 72 h. For miR-15a (green) and Fra-2 (blue), data were obtained by performing IPA® analyses on the genes significantly correlated with Fra-2 expression and the putative target genes inversely correlated with miR-15a levels in PDAC patients from the TCGA dataset. Histograms showing the significance of the five commonly activated pathways, as obtained by the Venn diagram. Dotted red lines indicate the established threshold of 1.5 of −log10(p value). Scatter plots representing the correlation of IGF1R expression with levels of miR-15a (b) and Fra-2 (c) in PDAC samples from the TCGA dataset. The number of analyzed samples (n), the Spearman correlation value (r), and its significance (p value) are reported in the graphs. Box plots showing the expression of Fra-2 (d) and IGF1R (e) in an independent cohort of 38 PDAC samples stratified according to miR-15a levels. miR-15a expression was assessed by qRT-PCR, Fra-2 and IGF1R were evaluated by immunohistochemistry and data represent the percentage of positive cells in each tumor. Unpaired t test was used for statistical analyses and asterisks indicate significant differences. **p < 0.01; ***p < 0.001. f Histograms showing miR-15a expression in patients from the lower quartile (in black) and from the upper quartile (in green). g Representative images of immunohistochemical staining of IGF1R and Fra-2 in PDAC samples stratified according to miR-15a levels, as shown in (f) (10x, magnification)